Biomedical subjects
Publications and source records attributed to J Kohyama.
OBJECTIVES: To examine the sleep-disordered breathing in patients with Freeman-Sheldon syndrome (FSS). MATERIAL AND METHODS: One night polysomnography was performed for 2 teenage FSS patients. RESULTS: They showed frequent obstructive sleep apnea exclusively during rapid-eye-movement sleep. CONCLUSION: FSS is a risk factor for the occurrence of sleep disordered breathing.
Whether the cerebral or subcortical lesions are involved in the pathogenesis in infantile spasms (IS) remains to be determined. To investigate the functional lesions of the subcortical structures in IS, the brainstem expression of neurotransmitters, neuropeptides and calcium-binding proteins in IS autopsy cases of lissencephaly and of perinatal hypoxic ischemic encephalopathy (HIE/IS) was investigated. The IS patients consisted of four subjects each of lissencephaly and HIE. They suffered from both West and Lennox-Gastaut syndromes. The healthy and disease controls were composed of four subjects without neuromuscular disorders and six cases of HIE (HIE/C), neither of whom had the epileptic syndrome. In these subjects the expressions of tryptophan hydroxylase (TrH), tyrosine hydroxylase (TH), parvalbumin (PV), methionine-enkephalin (ME) and substance P (SP) were immunohistochemically determined in serial sections of the midbrain, pons and medulla oblongata. The immunoreactivity of neurons and neuronal processes for TH was altered in the mesencephalic periaqueductal gray matter, locus ceruleus, and dorsal vagal nucleus in the patients. The HIE/IS cases showed reduced TrH-immunoreactivity in the medullary raphe nuclei. The brainstem auditory tract was poorly discernible on anti-PV immunostaining in the IS patients. The immunoreactivity for ME in the spinal trigeminal nucleus was severely affected in the IS patients, while that for SP was comparatively well preserved. It is suggested that the presence of common brainstem lesions in IS is irrespective of etiologies. It is intriguing that some of the changes seemed to be interrelated with the neurophysiological abnormalities being reported in IS patients.
Paradoxical inward rib cage movement in children is quantified by the labored breathing index (LBI) on the respiratory inductive plethysmography. Labored breathing index during rapid eye movement sleep (REMS) in 59 children without obvious sleep disordered breathing (SDB) declined with age, and decreased to the mature low level at 35 months of age. The LBI was also found to reflect well the severity of SDB. Paradoxical inward rib cage movement, which was quantified by LBI, is concluded to be an important finding in diagnosing SDB in child patients.
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OBJECTIVES: To assess the previously proposed hypothesis that enuretic patients have a dysfunction in the pontine reticular formation. METHODS: In 18 patients with intractable nocturnal enuresis, rapid eye movement (REM)-related phasic chin muscle activity loss in REM sleep was examined by means of a single-night polysomnography. RESULTS: In 5 of 18 patients, this physiologically seen phenomenon was found to be disturbed. CONCLUSIONS: Since REM-related phasic chin muscle activity loss is disturbed by the functional impairment in the pontine reticular formation, some enuretic patients could be considered as presenting a dysfunction in this structure.
One-night polysomnography was performed on seven subjects suffering from breath-holding spells, including one whose death was suggested to be a consequence of a breath-holding spell. The fatal case showed no rapid eye movements (REMs) during REM sleep, although he exhibited REMs during wakefulness. The average numbers of both REMs and bursts of REMs in REM sleep in the other six breath holders were significantly lower than those in age-matched controls. The breath holders showed no airway obstruction, desaturation, or sleep fragmentation. Since the rapid ocular activity in REM sleep is generated in the brain stem, we hypothesized that a functional brainstem disturbance is involved in the occurrence of breath-holding spells.
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PURPOSE: The phasic inhibition index (PII) is the rate of the simultaneous occurrence of rapid eye movement bursts (RBs) and phasic chin muscle activity (PCMA) during rapid eye movement sleep (REMS). PII is low insofar as physiologically occurring REM-related phasic inhibition acts on chin muscles. Previously we found that PII was significantly higher in patients with infantile spasms (ISs) who had a recurrence of convulsions than in patients with ISs who exhibited no recurrence. We aimed to predict the response of patients with ISs to conventional anticonvulsants (AEDs) by means of REMS components including PII, expecting to facilitate avoidance of potentially hazardous hormonal therapy. METHODS: REMS, recorded before the beginning of any medication, was retrospectively examined in 15 patients with ISs. The patients were classified into two groups according to the response to initial treatment with conventional AEDs. Conventional AEDs were enough to control the spasms in six good responders (GRs), whereas further hormonal therapy was required in nine poor responders (PRs) to control the spasms. RESULTS: The amount of REMS was significantly lower in patients with ISs than in controls. GRs had less REMS than did PRs, although no significant difference was observed. Although the frequencies of RB and PCMA showed no significant differences among GRs, PRs, and controls, the average PII value in PRs (12.6+/-3.4; mean+/-SD) was significantly (p < 0.001) higher than that in GRs (6.1+/-1.7). CONCLUSIONS: PII is a useful parameter for differentiating GRs from PRs.
OBJECTIVES: To study the functional development of neuronal systems that suppress muscle activity, we quantified the chronological change of atonia in rapid-eye-movement sleep (REMS). METHODS: REMS atonia was quantified by the tonic and phasic inhibition indices (TII and PII). TII indicates the shortness of chin muscle activity, whereas PII standardizes the simultaneous occurrence of chin muscle activity and bursts of rapid eye movements. TII and PII were calculated in REMS of 135 polysomnographical recordings obtained in healthy humans from premature babies to a 77-year-old man. RESULTS: TII increased significantly with age, while PII decreased significantly. TII reached an adult level at preadolescence, while PII at early infancy. CONCLUSION: Human nervous systems involved in both tonic and phasic inhibition in REMS raise their activities with age. Since TII and PII reach adult levels at different ages, suppression of muscle activity is hypothesized to be mediated through at least 2 independent systems in humans.
Xeroderma pigmentosum has been known to result from disturbance in the repair of injured DNA caused by the ultra violet light. According to cell fusion studies, this disease is classified into 8 groups. Among these groups, group A (A-XP) shows the most severe type of neurological disturbance. Slowly progressive diffuse impairment both in the central and the peripheral nervous systems has been reported. Although hearing loss occurs in all the patients, few papers have described the chronological changes of this disability. This study aimed to clarify the development of audiological abnormalities in A-XP patients. We recorded auditory brainstem evoked responses (ABRs) in 20 Japanese children with A-XP. All patients had homozygous intron 3 splicing mutations of xeroderma pigmentosum group A complementing gene, the most common type mutations in Japan. ABR threshold, peak latency of 5th wave and the peak interval latency between the 1st and 5th waves (I-V interpeak latency) were measured, and were compared with those obtained from age-matched controls. ABRs were well detected in all patients examined under 4 years old. The I-V interpeak latencies became shorter with age as in the controls. In 3 ears, the 5th wave was recorded without 1st wave. In 4 ears which no ABRs were detected with 90 dBHL stimulation, the only 5th wave was detected. No waves were obtained from the patients aged over 10 years. The current study revealed that ABR disturbance in A-XP patients became obvious after 4 years of age. In addition, no ABR was found to be identified after 10 years of age. During 4 to 10 years of age, some patients showed the elevation of the threshold of the 5th wave. In A-XP patients, the peripheral nerve was hypothesized to be affected earlier than the central pathway involved in ABR.
The pontomedullary region is responsible for the reduction of muscle activity in rapid-eye-movement sleep and contributes to the control of muscle tone in waking. This study sought to clarify the nature of the interaction between the pontine and medullary reticular formation in mediating muscle tone suppression. The degree of medullary-induced neck muscle tone suppression in the decerebrate cat was assessed before and after microinjection of lidocaine into the pontine reticular formation. Medullary stimulation-induced suppression of neck muscle tone was blocked after pontine lidocaine microinjection. The maximum blockade was observed at 16.6 minutes on average after the injection, and recovery occurred within 45 minutes. We conclude that descending mechanisms from the medulla are not sufficient for the triggering of muscle tone suppression. A two-way interaction between the medulla and pons is hypothesized to play a crucial role in the control of muscle tone.
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The pontomedullary region is responsible for both the tonic and phasic reduction of muscle activity in rapid-eye-movement sleep and contributes to the control of muscle tone in waking. This study focused on determining the time course of activity in the pontomedullary systems mediating atonia. Short-train stimulations (3 0.2-ms pulses at 330 Hz) of the pons and medulla suppressed neck and hindlimb muscle activity in decerebrate cats. We identified two distinct phases of suppression, early and late. The anatomic sites that produced each suppression were intermixed. We estimated the dividing value of the conduction velocity for reticulospinal projections responsible for early and late phases of hindlimb muscle tone suppression to be 22.8 m/s. In the medial medulla, 238 reticulospinal units, which send axons to the L1 level of the spinal cord, were identified. Pontine stimulation that suppressed hindlimb muscle tone increased the firing rate of 138 units (type I). Sixteen type I units showed a delayed response to the pontine stimulation with a latency of 10 ms or longer (type Id), whereas 122 type I units exhibited an earlier response (type Ie). Seven type Ie units had an axonal conduction velocity of <22.8 m/s, whereas the remaining 115 conducted at faster than 22.8 m/s. Early and late hindlimb muscle tone suppressions were hypothesized to be mediated through fast and slow conducting type Ie reticulospinal units. The activity of type Id neurons may contribute to the cessation of the early-phase suppression as well as to the induction, maintenance, or cessation of the late-phase suppression.
OBJECTIVE: To describe the age-related changes in the number of movements in rapid eye movement (REM) sleep, and to quantify the functional maturation of motor inhibition. STUDY DESIGN: Gross movements, phasic mentalis muscle activity (PMMA), and a new index that expressed the shortness of PMMA (the proportion of short PMMA among all PMMA) were examined cross-sectionally in 87 healthy children from premature babies to preadolescents by means of a single (all-night) polysomnography. RESULTS: The incidence of gross movements and long PMMA decreased with age, whereas that of short PMMA increased with age. The new index exhibited an age-related increase, with the highest correlation with age among sleep parameters examined, and reached an adult level after 6 years of age. CONCLUSION: We found that the age-related reduction of PMMA duration, which was expressed by a new index, occurred in parallel with the maturation of the inhibitory system that is tonically activated during REM sleep. We named this index the tonic inhibition index and concluded that the neuronal system involved in motor inhibition during REM sleep was still maturing during early childhood. We propose the tonic inhibition index as a useful quantitative indicator for the maturity of the inhibitory system.
To determine how thyroid hormone deficiency before birth influences early development of the human central nervous system, we examined sleep development in children with congenital hypothyroidism using all-night polysomnography. Although the sleep-wakefulness circadian rhythm was not disturbed, two patients under 1 year of age showed mild decreases of REM sleep. Rapid eye movements during REM sleep were significantly decreased in one patient in whom thyroxine replacement was delayed. Regarding phasic body movements during sleep, generalized gross movements were more frequently disturbed than localized muscle twitches, and even after L-thyroxine replacement, they were significantly reduced when compared with those in controls. Children with acquired hypothyroidism and neonatal transient hyperthyrotropinemia showed no severe abnormalities of the sleep parameters examined here. Sleep development in patients with congenital hypothyroidism is believed to be useful for regional evaluation of the brain impairment in congenital hypothyroidism.
Single polysomnography was performed before treatment in 17 patients with infantile spasms (IS) (13 with a cryptogenic type and 4 with a symptomatic one). Their sleep components during rapid eye movement (REM) sleep were compared with those in 22 age-matched controls. The tonic muscle atonia during REM sleep was observed in all IS patients as in controls. The amount of REM sleep in IS patients was significantly lower, while the incidences of gross movements, phasic chin muscle activity, and bursts of horizontal rapid eye movements were identical with those in controls. The phasic inhibition index (PII), i.e., the rate of simultaneous occurrence of phasic chin muscle activity and bursts of horizontal rapid eye movements, was significantly higher in IS than in controls. The PII value was the only parameter that reflected our patients' prognosis among the obtained REM sleep parameters. We presume that the elevated PII in IS reflects the weakness of the phasic motor activity reduction occurring with horizontal rapid eye movements, and attribute this disturbance to a functional instability of the rostral pontine tegmentum. We propose that PII is a useful parameter for assessing the prognosis of IS. Considering the neural basis for elevated PII in IS, this index is expected to provide a clue for explaining the pathophysiology of IS.
During rapid eye movement (REM) sleep, phasic and further motor inhibition occurs during clusters of REMs besides tonic motor inhibition. We describe the age-related quantitative change of the activity of this REM-related phasic motor inhibition. For this purpose, we introduced the phasic inhibition index (PII). PII is the rate of simultaneous occurrence of bursts of horizontal REMs and phasic mentalis muscle activity during REM sleep. We examined these phasic REM sleep parameters in 87 healthy children from premature babies to preadolescents. The incidence of bursts of REMs showed no age-related change, while that of the phasic mentalis muscle activity increased with age. The simple ratio between the incidence of bursts of REMs and that of phasic mentalis muscle activity showed no significant age-related change, whereas PII decreased rapidly during infancy and reached low constant values thereafter. We concluded that this age-related PII decline reflected the maturation of REM-related phasic motor inhibition. This is the first quantitative description on the development of human motor inhibition. Taken with the neuronal basis underlying REM-related phasic motor inhibition, we hypothesize that a PII value is within the normal low range as far as both the rostral pontine tegmentum and the brainstem inhibitory pathways are functionally intact.
In order to investigate the effect of hypothyroidism during the early development on the functional brainstem maturation, polysomnograms were recorded on 7 patients with congenital hypothyroidism detected by neonatal screening before treatment. The following two sleep indices for phasic muscle activity during rapid eye movement (REM) sleep were evaluated: dissociation index (DI) and % body movements in REMs burst (% BM). The DI is defined as the ratio of the number of twitch movements (TMs) during REM sleep to the sum of TMs and localized movements (LMs) during REM sleep. The % BM is the percentage of TMs and LMs which occur during bursts of REMs in relation to the sum of TMs and LMs during REM sleep. The DI and % BM can reflect maturation of the tonic and phasic inhibitory system functioning during REM sleep, respectively. In congenital hypothyroidism, DI was lower than that in controls, while % BM was identical. The tonic inhibitory system was specifically involved, whereas the phasic one was preserved. It is suggested that thyroid hormone could play an important role on the functional brainstem maturation. We propose to investigate their neuropsychological development over the long term to elucidate the influence of hypothyroidism.